Pegylated insulin-like growth factor-1 biotherapeutic delivery promotes rotator cuff regeneration in a rat model.

Pegylated insulin-like growth factor-1 biotherapeutic delivery promotes rotator cuff regeneration in a rat model.
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聚乙二醇化胰岛素样生长因子-1生物治疗递送促进大鼠模型中的肩袖再生。

DOI:
10.1002/jbm.a.37378
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发表时间:
2022-07
影响因子:
4.9
通讯作者:
Laurencin, Cato T.
Laurencin, Cato T.
中科院分区:
工程技术3区
文献类型:
--
作者:
Prabhath, Anupama;Vernekar, Varadraj N.;Esdaille, Caldon J.;Eisenberg, Ellen;Lebaschi, Amir;Badon, Mary;Seyedsalehi, Amir;Dzidotor, Godwin;Tang, Xiaoyan;Dyment, Nathaniel;Thomopoulos, Stavros;Kumbar, Sangamesh G.;Deymier, Alix;Weber, Eckhard;Laurencin, Cato T.

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由于肌腱及其末端的复杂、细胞少、血管少和运动活跃的性质,肌腱袖撕裂的修复具有挑战性。胰岛素样生长因子-1 (IGF-1)是一种很有前途的治疗方法。然而,其不稳定的性质、较短的半衰期和破坏体内平衡的能力限制了其临床应用。聚乙二醇化已被证明可以改善稳定性并维持体循环中的IGF-1水平,而不会破坏体内平衡。为了在修复后的肌腱中提供IGF-1的局部递送,我们在聚己内酯为基础的基质中封装了聚乙二醇化的IGF-1模拟物及其对照物(未聚乙二醇化的IGF-1模拟物和重组人IGF-1),并在临床前旋转袖修复的啮齿动物模型中对它们进行了评估。与对照组相比,聚乙二醇化的igf -1模拟递送在修复的8周内重建了肌腱到骨的特征结构,并改善了肌腱的拉伸性能,这表明聚乙二醇化在这种复杂的组织再生中的重要性。这些结果证明了一种简单和可扩展的生物传递技术替代组织源性移植物用于软组织修复。
Tears in the rotator cuff are challenging to repair because of the complex, hypocellular, hypovascular, and movement-active nature of the tendon and its enthesis. Insulin-like Growth Factor-1 (IGF-1) is a promising therapeutic for this repair. However, its unstable nature, short half-life, and ability to disrupt homeostasis has limited its clinical translation. Pegylation has been shown to improve the stability and sustain IGF-1 levels in the systemic circulation without disrupting homeostasis. To provide localized delivery of IGF-1 in the repaired tendons, we encapsulated pegylated IGF-1 mimic and its controls (unpegylated IGF-1 mimic and recombinant human IGF-1) in polycaprolactone-based matrices and evaluated them in a pre-clinical rodent model of rotator cuff repair. Pegylated-IGF-1 mimic delivery reestablished the characteristic tendon-to-bone enthesis structure and improved tendon tensile properties within 8 weeks of repair compared to controls, signifying the importance of pegylation in this complex tissue regeneration. These results demonstrate a simple and scalable biologic delivery technology alternative to tissue-derived grafts for soft tissue repair.
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